Our previous studies have shown that angiotensin II increases carbonic anhydrase activity both in vitro and in vivo. In this study we investigated in vitro the effect of angiotensin II on carbonic anhydrase I and II from erythrocytes and on arteriolar vascular smooth muscle carbonic anhydrase I. We also studied in vitro and in vivo the effect of angiotensin II receptor blockers (irbesartan and candesartan) on purified carbonic anhydrase I and II, on vascular smooth muscle carbonic anhydrase I and on arterial blood pressure in humans and in animals. In vitro results showed that angiotensin II is a direct and stronger activator of carbonic anhydrase I than II. Angiotensin II receptor blockers reduced mainly carbonic anhydrase I activity and completely antagonized the activating effect of angiotensin II both on purified and on vascular smooth muscle carbonic anhydrase I. Our in vivo experiments showed that irbesartan and candesartan are powerful inhibitors of carbonic anhydrase I both in erythrocytes (in humans) and in vascular smooth muscles (in animals). In humans, irbesartan and candesartan progressively reduce arterial blood pressure in hypertensive subjects, in parallel with progressive reduction of erythrocyte carbonic anhydrase I activity. We believe that angiotensin II could have a dual mechanism of action: (1) angiotensin interacting with its receptor to form a stimulus-receptor complex; (2) the same stimulus directly acts on the carbonic anhydrase I isozyme (which might be coupled with angiotensin II receptors), ensuring an adequate pH for stimulus-receptor coupling for signal transmission into the cell and hence vasoconstriction.
Lp(a) is a unique class of lipoprotein particles that exhibits a considerable size heterogeneity resulting from the size polymorphism of apo(a), its unique protein component. An elevated level of Lp(a) in plasma has been proposed to be a risk factor for premature development of coronary artery disease. To evaluate the relationship between Lp(a) concentration and apo(a) isoform size with restenosis after percutaneous transluminal coronary angioplasty, Lp(a) levels and apo(a) phenotypes were determined in 204 patients who underwent a successful coronary angioplasty procedure and stent implantation. The patients were followed with clinical examinations and exercise tests at 1, 3, and 6 months, and a control coronary angiography was performed after 6 months to evaluate restenosis. Lp(a) levels were determined with an ELISA that is insensitive to the size heterogeneity of Lp(a), and the apo(a) isoforms were determined by a high-resolution agarose gel electrophoresis method followed by immunoblotting with a specific monoclonal antibody. Of the 146 patients who underwent angiographic evaluation, 57 (39%) had restenosis, whereas 89 (61%) did not. Lp(a) levels and the distribution of the expressed apo(a) phenotypes were compared in these two groups of patients. Although the mean and median Lp(a) levels were higher in the restenosed group, the difference was not statistically significant. However, a significant difference in Lp(a) values was found in women (P=0.043), even though, because of the small number of women in the study (n=35), no sound conclusions can be reached on the predictive role of Lp(a) in restenosis. There also was no difference in the distribution of apo(a) phenotypes between the two groups. Because of their wide distribution, Lp(a) values and apo(a) isoforms do not seem to be a useful indicator of risk of restenosis after percutaneous transluminal coronary angioplasty in our study cohort.
Bovine seminal ribonuclease is a member of the RISBAses (ribonucleases with special biological actions) family. It exerts specific anti-tumor, embryotoxic, aspermatogenic and immunosuppressive activities. The cytotoxic effect of bovine seminal ribonuclease on tumor cells is accompanied by the induction of apoptosis. We provide ultrastructural and flow cytometry evidence of apoptotic death following bovine seminal ribonuclease treatment, in normal cells and phytohemagglutinin-stimulated lymphocytes. Transmission and scanning electron microscopy, which were fully supported by flow cytometry data, showed typical features of apoptosis, such as decreased cell size, chromatin condensation, fragmentation in micronuclei, and the presence of apoptotic bodies.
The positive results obtained with cyclosporine-A both in an experimental model and in selected patients with advanced systemic lupus erythematosus support the hypothesis that the drug could be used as a steroid sparer in the earliest stages of active disease. To determine the 12-month clinical efficacy (disease control and steroid sparing), safety, and tolerability of low-dose cyclosporine-A plus steroids versus steroids alone, we designed a multicenter, open, prospective, randomized, pilot study, controlled for parallel groups. The patients were then followed up to month 24. A total of 18 consenting patients with recently diagnosed systemic lupus erythematosus of moderate severity indicated for the use of steroids in acute boluses and subsequently per os were enrolled at two university hospital medical centers. The protocol was based on three 1-g boluses of 6-methyl-prednisolone followed by cyclosporine-A (<5 mg/kg per day) plus prednisone 0.5–1 mg/kg per day per os, reduced by 5 mg/day every 2 weeks following clinical remission, versus the same doses of oral prednisone alone. The efficacy evaluation was based on a four-point scale (from absent/none to severe) for signs and symptoms of systemic lupus erythematosus and immunoserological parameters. The disease activity index and cumulative prednisone dose per patient were analyzed. Any adverse events were reported. All patients showed a reduction in disease activity index within the 1st month. The results were significantly better in the group with cyclosporine-A plus prednisone throughout month 12 (baseline and 12-month disease activity indexes: 21.3±8.6 and 5.0±2.5 versus 20.4±7.1 and 8.8±6.0 in the prednisone group,P<0.05). The 12-month cumulative mean dose of prednisone was significantly lower in the group with both cyclosporine-A plus prednisone (179.4±40.1 versus 231.8±97.1 mg/kg,P<0.005). No unusual adverse events related to the study drugs have been reported. In particular, renal function and blood pressure monitoring revealed no significant changes from mean baseline values in either group. No disease flares were reported in the group treated with cyclosporine-A plus prednisone during the 12- to 24-month period. Thus cyclosporine-A represents a useful corticosteroid sparer in the maintenance of clinical remission in patients with an early-stage, active systemic lupus erythematosus.
The study of the stability of saturated mono-, or polyunsaturated fatty acids, both esterified and not esterified, in plasma, circulating cells, and tissues is extremely important to validate the use of biological samples stored at low temperature in “biological banks”, which are used for experimental, observational, dietary, or pharmacological studies. Since red blood cells are easily accessible cells, they are used as a marker of less-accessible tissues, especially in large-scale epidemiological studies. Data from the literature suggest that the addition of an antioxidant and the freezing of red blood cells do not cause any variation in the fatty acid composition for a period of 2–6 months up to 1 year. We evaluated the fatty acid concentration in red blood cells isolated from venous blood samples of one subject, preserved with butylated hydroxytoluene and N 2 and stored at −80°C for up to 2 years. Erythrocytes of venous samples of six subjects stored at −20°C for 6 months without butylated hydroxytoluene and in the presence of air were used for comparison purposes. Our data demonstrate that a long storage time (2 years) does not significantly influence the erythrocyte fatty acid concentration when using very low temperatures (−80°C) and antioxidants (butylated hydroxytoluene) in the presence of N 2 .
The aim of the present study was to assess the endothelial function of the microcirculation in chronic renal failure. We investigated the responses of the cutaneous blood flow to locally delivered acetylcholine and sodium nitroprusside in uremic patients. The study included 60 chronic uremic patients: 40 patients with a creatinine clearance of 4–25 ml/min were on conservative treatment and 20 patients were on maintenance hemodialysis. The changes in skin blood flow following ionotophoretic delivery of acetylcholine (an endothelium-dependent vasodilator) and sodium nitroprusside (an endothelium-independent vasodilator) were measured by laser Doppler flowmetry. Acetylcholine induced a progressive increase in blood flow in both groups, reaching approximately 100% of the maximal hyperemic response obtained by sodium nitroprusside delivery. The percent increase in blood flow from baseline was lower in hemodialysis patients than in patients on conservative treatment, after both acetylcholine (550±44 vs. 718±61%,P<0.05) and sodium nitroprusside (553±46 vs. 735±69%,P<0.05) delivery. In the hemodialysis group, the hyperemic responses to acetylcholine and sodium nitroprusside did not improve after the hemodialysis session. Hence, the hyperemic responses of the skin microcirculation are lower in hemodialysis patients than in patients on conservative treatment, and did not ameliorate after hemodialysis. It seems to be independent of endothelial dysfunction, and associated with the severity of uremia and with the maintenance hemodialysis treatment. This microcirculatory abnormality is in keeping with the arterial stiffness and vascular wall damages described in dialysis patients, which contribute to the cardiovascular morbidity of chronic uremia.
In the present study, a new functional test for the detection of increased resistance of coagulation factor V to degradation by activated protein C (factor V Leiden mutation) was evaluated. The STA-STACLOT APC-R Test (Diagnostica Stago, Asnieres, France) is based on the specific activation of factor X by Crotalus viridis helleri snake venom. The results are given as clotting time in seconds of the patient’s plasma in the presence of venom and activated protein C. The intra-assay coefficient of variation was 2.17% ( n =20) for samples within the normal range, and 1.70% and 1.42% ( n =20) for the plasma of a heterozygous or a homozygous carrier of the factor V Leiden mutation, respectively. The inter-assay coefficient of variation ( n =10) was 7.75% for the plasma of a healthy donor, 5.05% for the plasma of a heterozygous carrier and 3.38% for the plasma of a homozygous individual. The normal range (5th–95th percentile) of 136.4 s–174.7 s was derived from the clotting time of the plasma of 38 healthy controls. Values below 136 s were found in every sample from patients carrying the factor V Leiden mutation ( n =52), whereas no patient with protein C ( n =11) or protein S deficiency ( n =10) had reduced clotting times. Homozygous carriers of the factor V Leiden mutation had clotting times shorter than 66.0 s and heterozygous carriers had clotting times longer than 80.0 s. Thus, based upon the individual clotting time, patients homozygous for factor V Leiden mutation could easily be distinguished from normals or heterozygous individuals. The influence of coagulation factor X, V, or II deficiency on the STACLOT APC-R Test was evaluated and revealed prolonged clotting times at factor V activities below 50%. In the presence of lupus anticoagulant the specificity of the STA-STACLOT APC-R Test was clearly decreased. In the present study, we clearly show that the STA-STACLOT APC-R Test is able to discriminate carriers of the factor V Leiden mutation from healthy controls or patients with protein C or protein S deficiency.
The present study was designed to investigate whether oxidized low-density lipoprotein is accumulated in the left and right ventricular walls of patients with coronary heart disease (n=10) compared with patients with dilated cardiomyopathy (n=9) or healthy heart donors (controls, n=5). Sections from both ventricles of explanted hearts and coronary arteries of the same patients were analyzed by semiquantitative immunohistochemistry for the presence of oxidized low-density lipoprotein. Oxidized low-density lipoprotein was enriched in the left and right ventricular walls from coronary heart disease patients compared with patients with dilated cardiomyopathy (P=0.0012 for left ventricle and P=0.103 for right ventricle) or controls (P=0.0012 for the left ventricle and P<0.05 for the right ventricle). The accumulation of oxidized low-density lipoprotein was higher in the left than in the right ventricles in all three groups. Positive immunoreactivity for oxidized low-density lipoprotein was mainly identified in the endocardium and the subendocardial areas of the ventricles and co-localized with macrophages. Accumulation of oxidized low-density lipoprotein in the ventricles significantly correlated with the enrichment in the respective coronary arteries, whereas only poor correlations were observed between various hemodynamic parameters and ventricular oxidized low-density lipoprotein accumulation. Ventricular accumulation of oxidized low-density lipoprotein seems to be a generalized pathophysiological process which does not exclusively involve the coronary arteries. Higher oxidative stress in combination with impaired oxygen supply in the endocardium could have favored low-density lipoprotein deposition and oxidation.
Stress, a common phenomenon in today's society, is suspected of playing a role in the development of disease. Stressors of various types, psychological, physical, and biological, abound. They occur in the working and social environments, in air, soil, water, food, and medicines. Stressors impact on cells directly or indirectly, cause protein denaturation, and elicit a stress response. This is mediated by stress (heat-shock) genes and proteins, among which are those named molecular chaperones because they assist other proteins to achieve and maintain a functional shape (the native configuration), and to recover it when partially lost due to stress. Denatured proteins tend to aggregate and precipitate. The same occurs with abnormal proteins due to mutations, or to failure of post-transcriptional or post-translational mechanisms. These abnormal proteins need the help of molecular chaperones as much as denatured molecules do, especially during stress. A cell with normal antistress mechanisms, including a complete and functional set of chaperones, may be able to withstand stress if its intensity is not beyond that which will cause irreversible protein damage. There is a certain threshold that normal cells have above which they cannot cope with stress. A cell with an abnormal protein that has an intrinsic tendency to misfold and aggregate is more vulnerable to stress than normal counterparts. Furthermore, these abnormal proteins may precipitate even in the absence of stress and cause diseases named proteinopathies. It is possible that stress contributes to the pathogenesis of proteinopathies by promoting protein aggregation, even in cells that possess a normal chaperoning system. Examples of proteinopathies are age-related degenerative disorders with protein deposits in various tissues, most importantly in the brain where the deposits are associated with neuronal degeneration. It is conceivable that stress enhances the progression of these diseases by facilitating protein unfolding and misfolding, which lead to aggregation and deposition. A number of reports in the last few years have described research aimed at elucidating the role of heatshock proteins, molecular chaperones in particular, in the pathogenesis of neurodegenerative disorders. The findings begin to shed light on the molecular mechanism of protein aggregation and deposition, and of the ensuing cell death. The results also begin to elucidate the role of molecular chaperones in pathogenesis. This is a fascinating area of research with great clinical implications. Although there are already several experimental models for the study of proteinopathies, others should be developed using organisms that are better known now than only a few years ago and that offer unique advantages. Use of these systems and of information available in databases from genome sequencing efforts should boost research in this field. It should be possible in the not-too-distant future to develop therapeutic and preventive means for proteinopathies based on the use of heat-shock protein and molecular chaperone genes and proteins.
Adhesion molecules play a role in the inflammation and pathogenesis of vascular diseases. In 13 patients with primary Raynaud’s phenomenon, 19 with Raynaud’s phenomenon associated with connective tissue disease, and 16 control subjects, we measured plasma levels of soluble forms of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, and von Willebrand factor. Patients with secondary Raynaud’s phenomenon had plasma levels of soluble forms of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, and von Willebrand factor which were significantly higher than in those with primary Raynaud’s phenomenon and controls, while no difference was observed between patients with primary Raynaud’s phenomenon and controls. Within the group with secondary Raynaud’s phenomenon, the strongest correlations were between soluble forms of intercellular adhesion molecule-1 and both E-selectin, (r=0.67,P<0.001) and von Willebrand factor (r=0.58,P<0.01). In none of the three groups were the levels of soluble adhesion molecules and von Willebrand factor changed by exposure of hands to cold, although all patients had a definite vasospasm. In conclusion, this study indicates that primary Raynaud’s phenomenon is not associated with elevation of soluble adhesion molecules and von Willebrand factor. Prospective studies are now required to investigate the role of these molecules as predictors of secondary diseases.
The role of circulating endothelin-1, a potent vasoconstricting peptide, in liver cirrhosis is still controversial. It has been postulated that endothelin-1 may play a role in the circulatory derangement occurring in cirrhotic subjects, and increased plasma endothelin-1 levels have been reported in these patients. In this study we looked for a relationship between the severity of the liver disease according to Child’s classification and plasma endothelin-1 concentrations in a group of cirrhotic patients compared with a healthy control group. Twenty-two cirrhotic patients and 10 healthy controls, matched for sex and age, were selected for study after informed consent. The etiology of cirrhosis was posthepatitis B in 8 of 22 cases, posthepatitis C in 13 of 22 cases, and alcoholism in 1 patient. According to Child’s classification, 6 patients were in class A, 6 in class B, and 10 in class C. Plasma endothelin-1 was measured by a commercial RIA kit (Amersham UK). Mean±SD plasma endothelin-1 levels were 8.8±0.9 pg/ml in controls and 9.2±1.1 pg/ml in all cirrhotic patients (P>0.05). In each subgroup of cirrhotics, plasma endothelin-1 was 8.6±1.2 pg/ml in Child A, 8.9±1.9 pg/ml in Child B, and 10.6±1.5 pg/ml in Child C groups, respectively. There were no statistical differences between control subjects and Child A and B cirrhotic patients (P>0.05). A significant increase in endothelinl was observed only in the Child C group versus either group A or B (P=0.004). Our results show that alterations of circulating endothelin-1 do not occur in all cirrhotic patients; higher plasma levels than controls are only detectable in patients with more-severe hepatic failure. We do not know whether increased endothelin-1 levels are a consequence of hemodynamic disorders occurring in the advanced phase of liver cirrhosis or play a pathogenic role.
It has been shown that the β (C-C) chemokines macrophage inflammatory protein-1α/β (MIP-1α/β) and RANTES, which are released by CD8+ T cells, are potent inhibitors of HIV viral replication in vitro. To investigate whether serum concentrations of these chemokines reflect such a protective effect in vivo, we measured these in peripheral blood of 60 HIV seropositive patients, 10 healthy subjects, and 10 disease controls. Values were compared with the CDC disease stages and immunological surrogate markers of disease progression, such as CD4+ count, β2-microglobulin and 5′-neopterin serum levels. In addition, HIV RNA was measured in sera. All three chemokines were not significantly different between HIV patients and healthy individuals, nor were differences of chemokine levels between the CDC stages significant. Instead, disease controls exhibited significantly more MIP-1α and MIP-1β than normals or HIV patients. Furthermore, within the HIV-seropositive subjects we did not observe any relationship with the surrogate markers of HIV disease, CD4+ count, CD4+/CD8+ ratio, β2-microglobulin, and 5′-neopterin (all correlations NS). HIV viral load did not correlate with the measured chemokine concentrations (r<0.1, NS). In conclusion, endogenous levels of MIP-1α, MIP-1β, and RANTES do not reflect the hypothesized protective effect on disease progression in HIV infection. Thus, despite potential beneficial effects of the investigated chemokines, other factors may equally contribute to HIV replication control in vivo.
An excess of cardiovascular morbidity has been related to low birthweight. The aim of this study was to evaluate the relationship between low birthweight and levels of fibrinogen, lipoprotein(a), and albumin excretion rate, which are known risk factors for coronary artery disease. Seventy-two twins, with the same within-pair gender and normal glucose tolerance, were analyzed in order to avoid confounding factors, such as gestational age, birth order, or sex. Twins with the highest birthweights within the couple showed no significant difference of fibrinogen, lipoprotein(a), and albumin excretion rates compared with the twins with the lowest birthweights among the two co-twins. Moreover, no relevant correlation was found between birthweight and intra-pair birthweight differences and fibrinogen, lipoprotein(a), and albumin excretion rates. The lack of correlation between fibrinogen, lipoprotein(a), albumin excretion rate and birthweight, suggests that these factors do not contribute to the link between intrauterine malnutrition and increased cardiovascular risk.
Thrombosis is a complication of atherosclerosis and monocytes play a determinant role either in the progression of atherosclerotic plaque or in blood coagulation by way of tissue factor expression. Platelets play a direct role in thrombosis and a hyperfunctional state has been described in hypercholesterolemic subjects. Moreover, platelets seem to be able to enhance monocyte activity. Cholesterol-lowering molecules (statins) are reported to reduce cardiovascular risk, either by decreasing the circulating level of cholesterol or by non-lipidic actions such as the reduction of monocyte and platelet activity. The aim of our study was to investigate the influence of platelets on the expression of tissue factor by monocytes and the effect induced by cerivastatin. We measured tissue factor levels by ELISA and the procoagulant activity of stimulated monocytes by a clotting assay on cellular preparations and whole blood in 40 hypercholesterolemic subjects (22 male, 18 female, mean age 52.7±12 years, total cholesterol 251.6±19.9 mg/dl) before and after cerivastatin addition. Tissue factor expression was enhanced in hypercholesterolemic subjects compared with normal subjects (31.6±7.6 vs. 23±5.8 pg/cells,P<0.01). The presence of platelets increased the amount of tissue factor (55.3±7.3 pg/cells,P<0.001) and cerivastatin reduced the expression of tissue factor in isolated monocytes, in the mixed cellular system, and in whole blood (19.6±4.1 pg/cells,P<0.001). In conclusion, tissue factor expression by monocytes is enhanced in hypercholesterolemic subjects compared with normal controls. Platelets enhance monocyte production of tissue factor, and cerivastatin is able to counteract this prothrombotic mechanism.
The phagocyte-derived enzyme myeloperoxidase has been recently implicated in the pathogenesis of atherosclerosis, because it catalyzes the reaction of hydrogen peroxide with chloride ions to give the highly toxic oxidant hypochlorous acid. The aim of this study was to determine the dependence of this reaction on the concentration of hydrogen peroxide and of the enzyme by means of the photometric monochlorodimedone assay. The initial rate of hypochlorous acid formation increased less than proportionally with increasing myeloperoxidase concentrations. Variation of the concentration of hydrogen peroxide had a biphasic effect, with an optimal concentration of hydrogen peroxide. Above this concentration enzyme destruction is apparently predominant. The progress curves of hypochlorous acid formation showed two distinct maxima. It was concluded that hypochlorous acid not only reacts with monochlorodimedone but also with the amino groups of myeloperoxidase to form intermediary chloramines that may further chlorinate monochlorodimedone. This was supported by the kinetics in the presence of the amino compound glycine, a competitive substrate for chlorination by hypochlorous acid. In the presence of high concentrations of glycine the progress curve rises continuously, yielding a greatly increased concentration of chlorinating species, either hypochlorous acid or chloramines. We concluded that glycine protects myeloperoxidase against hypochlorous acid-induced self-destruction.
The detection of cardiac troponins in peripheral blood as protein markers of myocardial infarction is a new diagnostic tool in the diagnosis of cardiac disease. In order to increase the sensitivity and specificity of this diagnostic approach, a reverse transcription polymerase chain reaction assay has been developed to detect the mRNA encoding cardiac troponin I from myocardial cells hypothetically released from damaged cardiac tissue. The detection is specific for cardiac troponin I mRNA, with no amplification of homologous sequences of other troponin I isoforms, i.e., troponin I from skeletal muscle cells. However, a strong amplification signal for cardiac troponin I mRNA was detected in samples of peripheral blood from healthy human volunteers. In patients with acute myocardial infarction or angina pectoris, the cardiac troponin I mRNA levels were not increased over background levels. In conclusion, a reverse transcription polymerase chain reaction approach based on the amplification of cardiac troponin I mRNA is not feasible in the diagnosis of cardiac diseases.
Autoantibodies to the islet cell 65-kilodalton isoform of glutamic acid decarboxylase (GAD65) are present in most patients with type 1 diabetes mellitus years before the clinical manifestation of the disease. GAD65 autoantibodies are also present in a subset of patients with type 2 diabetes who frequently become insulin dependent. In the present study, we evaluated a new, commercially available radioimmunoprecipitation assay for measuring GAD65 autoantibodies using 125 I-labelled human recombinant GAD65. Results obtained with this assay were compared with those obtained by a reference assay based on 35 S-labelled recombinant GAD65. Analyses were performed on 67 patients with type 1 diabetes, 350 with type 2 diabetes, and 150 apparently healthy individuals. An excellent agreement was found between the results obtained by the 125 I-GAD65 assay and those obtained by the reference method. The receiver operating characteristic (ROC) curve analysis was used to evaluate the sensitivity and specificity of the two assays. The sensitivity of each assay was determined from the results of the 67 type 1 patients, while the specificity was based on the 150 healthy individuals. Based on the ROC curves, the two assays appeared identical, with a sensitivity of 84% and a clinical specificity of 98%. In conclusion, based on our results, this simple, one-step centrifugation, high-capacity 125 I-GAD65 assay has the same sensitivity and specificity as the reference assay and is highly suitable to detect GAD65 autoantibodies in human samples.
Anticardiolipin antibodies are found frequently in those suffering from migraine, but it is not clear if this association is real or coincidental. Moreover, there are no data on the prevalence of anticardiolipin antibodies in children. In this study, 40 patients were divided into two groups according to the type of migraine: group I included 22 cases (15 females and 7 males, mean age±SD 13.7±8.9 years) suffering from migraine with and without aura; group II consisted of 18 children (10 females and 8 males, age 14.7±6.9 years) having migraine with prolonged aura or migrainous infarction, also called complicated migraine. We studied two groups of children as controls: a group of 35 children (25 females and 10 males, mean age 13.9±7.1 years) with juvenile chronic arthritis (group III) and a group of 40 healthy sex- and age-matched children who did not suffer from migraine or any other neurological disease (group IV). No statistically significant differences in levels of anticardiolipin antibodies were found between group I and II and controls. Our data demonstrate that, in children with migraine, anticardiolipin antibodies are not more frequent than in healthy controls, and suggest that anticardiolipin antibodies are not implicated in the pathogenesis of migraine.
The association of cancer with low serum total cholesterol is well established. Less clear is the relationship of cancer with the cholesterol distribution among the different lipoprotein classes. Conflicting results have been reported on low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and serum triglyceride levels in different types of tumor. Total serum cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, and serum triglycerides were analyzed in 530 patients with newly diagnosed cancer (97 with hematological malignancies, 92 with tumor of the lung, 108 of the upper digestive system, 103 of colon, 32 of breast, and 98 of the genitourinary system) and in 415 non-cancer subjects. Anthropometric (body mass index) and biochemical (serum albumin) indices of nutritional status were also determined in all subjects. Total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, serum albumin, and body mass index were significantly lower in cancer than in non cancer-subjects. The lowest values of total cholesterol, low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol were recorded in patients with hematological malignancies and the highest in patients with breast tumor. All the cancer groups, with the exception of women with breast cancer, showed significantly lower total cholesterol, low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol than age- and sex-matched non-cancer subjects. Multiple regression analysis with low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, and triglycerides as dependent variables and sex, age, body mass index, albumin, and cancer (dummy variable) as independent variables, showed that cancer was independently associated with low levels of low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol and with high values of serum triglycerides. Total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, serum triglycerides, body mass index and serum albumin were significantly lower in patients with metastatic than in patients with non-metastatic solid tumor. The significant difference in low-density lipoprotein-cholesterol and serum triglycerides between patients with metastatic and non-metastatic cancer was lost when lipoprotein cholesterol and serum triglyceride levels were adjusted for nutritional variables. The lipid profile in cancer patients is characterized by low low-density lipoprotein-cholesterol, low high-density lipoprotein-cholesterol and relatively high serum triglycerides. The abnormality is a common feature of both hematological and solid tumors and is not entirely explained by poor nutrition.
